Weight matrices for protein-DNA binding sites from a single co-crystal structure.

@article{citeulike:3040172, abstract = {Transcription-factor proteins bind to specific DNA sequences to regulate gene expression in cells. DNA-binding sites are often identified using weight matrices calculated from multiple known binding sites. However, in many cases the number of examples is limited. Here, we report on an atomistic method that starts from an x-ray co-crystal structure of the protein bound to one particular DNA sequence, and infers other binding sites, which are used to construct a weight matrix. The emphasis of the paper is on using the Wang-Landau Monte Carlo algorithm to efficiently sample high-affinity binding sites, which demonstrates that sampling can produce accurate weight matrices in analogy to bioinformatics approaches. For cases of low complexity, we compare to the exhaustive (but slow) dead-end elimination algorithm. To recover crystal binding sites, it is important to include bound water in the protein-DNA interface. Our approach can, in principle, even be applied when no native protein-DNA co-crystal structure is available, only the structure of a closely related homologous protein whose amino-acid sequence is changed to the protein of interest.}, address = {NEC Laboratories America, Inc., Princeton, New Jersey 08540, USA. rendres@princeton.edu}, author = {Endres, R. G. and Wingreen, N. S. }, citeulike-article-id = {3040172}, issn = {1539-3755}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, keywords = {protein\_dna}, month = {June}, number = {6 Pt 1}, posted-at = {2008-07-24 16:01:11}, priority = {2}, title = {Weight matrices for protein-DNA binding sites from a single co-crystal structure.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16906878}, volume = {73}, year = {2006} }

TY - JOUR ID - citeulike:3040172 L3 - citeulike-article-id:3040172 TI - Weight matrices for protein-DNA binding sites from a single co-crystal structure. JF - Physical review. E, Statistical, nonlinear, and soft matter physics VL - 73 IS - 6 Pt 1 AD - NEC Laboratories America, Inc., Princeton, New Jersey 08540, USA. rendres@princeton.edu SN - 1539-3755 N2 - Transcription-factor proteins bind to specific DNA sequences to regulate gene expression in cells. DNA-binding sites are often identified using weight matrices calculated from multiple known binding sites. However, in many cases the number of examples is limited. Here, we report on an atomistic method that starts from an x-ray co-crystal structure of the protein bound to one particular DNA sequence, and infers other binding sites, which are used to construct a weight matrix. The emphasis of the paper is on using the Wang-Landau Monte Carlo algorithm to efficiently sample high-affinity binding sites, which demonstrates that sampling can produce accurate weight matrices in analogy to bioinformatics approaches. For cases of low complexity, we compare to the exhaustive (but slow) dead-end elimination algorithm. To recover crystal binding sites, it is important to include bound water in the protein-DNA interface. Our approach can, in principle, even be applied when no native protein-DNA co-crystal structure is available, only the structure of a closely related homologous protein whose amino-acid sequence is changed to the protein of interest. KW - protein_dna AU - Endres, RG AU - Wingreen, NS PY - 2006/06// UR - http://view.ncbi.nlm.nih.gov/pubmed/16906878 ER -